OVERALL OBJECTIVE: To determine the relation of the brain, particularly the hypothalamus, to development and growth of mammary and pituitary tumors, and to utilize this information to inhibit development and growth of mammary and pituitary tumors. Since prolactin and estrogen are the principal hormones involved in development and growth of mammary tumors, and to a large extent of pituitary tumors, and since these hormones are controlled directly (PRL) or indirectly (estrogen) by the hypothalamus, our aim is to experimentally alter hypothalamic function (by placing lesions or implanting hormones and drugs in the hypothalamus, by administration of drugs and hormones systemically and by use of appropriate environmental stimuli) to inhibit or accelerate development and growth of these tumors in mice, rats and dogs. The effects of high and low fat diets, reduced caloric intake and hypothalamic induced obesity on development and growth of mammary tumors, and on serum hormone levels, will be tested. The neuroendocrine mechanisms whereby pregnancy and lactation influence mammary tumor growth will be investigated. The effects of hypothalamic factors, hormones and drugs on hormone secretion and growth of pituitary tumors also will be studied. Old female rats also will be utilized since they develop spontaneous mammary and pituitary tumors, which we believe are related to functional changes in hypothalamic functions in old rats. We hope that some of the knowledge gained from these studies will prove useful in developing treatments for inhibiting the onset and/or growth of mammary and pituitary tumors in human subjects.